Identifying the mechanism of VATER association by developmental-stage specific administration of adriamycin

通过发育阶段特异性施用阿霉素来确定 VATER 关联机制

• 批准号: 20790773
• 负责人: NAITO Yoko
• 金额: $ 2.16万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790773/
• 关键词: VATER連合; アドリアマイシン; ニワトリ胚; caudal eminence; 前腸

VATER association represents a cluster of Vertebral, Anal, Tracheo-Esophageal, Radial and Renal malformations, and caudal regression syndrome is an entity consisting of a spectrum of congenital anomalies of lower spine and hips ssociated with genitourinary and lower limb defects. The concurrence of various malformations may be explained by a common defect in blastogenesis, but direct evidence is yet to be accumulated. Here, by the use of autofluorescence and the teratogenic effect of adriamycin, we demonstrated that adriamycin administered to eggs of White Leghorns distributes to the caudal portion of the embryo and foregut epithelium and induces caudal regression and tracheal and pulmonary agenesis. The induction of caudal regression syndrome-like anomaly was developmental stage and dose dependent. Embryos with caudal regression demonstrated tracheoesophageal anomalies, one of the defects included in VATER association. The stages at which anomalies were produced corresponded to that of human embryos between days 22 and 26 (Carnegie stages 10-11). In view of the antitumor activity of adriamycin by intercalating to double-stranded DNA of undifferentiated cells undergoing rapid cell division, it is possible that adriamycin had preferentially attacked cells in the caudal end where pronounced proliferation takes place during this narrow period of greatest susceptibility.

Vater缔合代表椎骨，肛门，气管管道，径向和肾脏畸形的群集，尾声回归综合征是一个由下脊柱的先天性异常和臀部与泌尿生殖率和下肢缺陷相结合的实体。各种畸形的同意可能是通过囊泡发生中的常见缺陷来解释的，但直接证据尚未积累。在这里，通过使用自动荧光和adrimycin的致畸作用，我们证明了给白色leghorns卵的阿霉素分布在胚胎和前肢上皮的尾部部分，并诱导凝固性回归，并诱发凝乳症和气管和肺病。尾声综合征样异常的诱导是发育阶段和剂量依赖性的。具有尾声回归的胚胎表现出气管食管异常，这是Vater关联中的一个缺陷之一。产生异常的阶段与第22至26天之间的人类胚胎相对应（卡内基阶段10-11）。鉴于阿霉素的抗肿瘤活性是通过将经历快速细胞分裂的未分化细胞的双链DNA进行插入的，因此在这种狭窄的最大敏感性的狭窄时期内，阿霉素可能在尾端中优先攻击了尾部的细胞，在这种尾部发生了明显的增殖。

项目成果

Caudal regression and tracheoesophageal malformation induced by adriamycin : A novel chick model of VATER association

阿霉素诱导的尾部退化和气管食管畸形：VATER关联的新型雏鸡模型

• 发表时间: 2009
• 期刊: Pediatric Research Feb 11
• 作者: Masayuki Miwa;Satoshi Kusuda;Kazushige Ikeda;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之;Masayuki Miwa;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之(編集河井昌彦);Yoko Naito;Yoko Naito
• 通讯作者: Yoko Naito

Caudal regression and tracheoesophageal malformation induced by adriamycin: A novel chick model of VATER association

阿霉素诱导的尾部退化和气管食管畸形：一种新型 VATER 关联雏鸡模型

• 发表时间: 2009
• 期刊: Pediatric Research
• 影响因子: 3.6
• 作者: Masayuki Miwa;Satoshi Kusuda;Kazushige Ikeda;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之;Masayuki Miwa;三輪雅之;三輪雅之;三輪雅之;三輪雅之;三輪雅之(編集河井昌彦);Yoko Naito
• 通讯作者: Yoko Naito